Apcin is a small cell-permeable APC/C inhibitor that blocks the interaction between APC/C and Cdc20 or Cdh1, with a KD value of 236µM for Cdc20[1]. Apcin occupies the D-box-binding pocket on the side face of the WD40-domain of Cdc20 protein, competitively inhibiting binding of Cdc20 to the ubiquitylation of D-box-containing substrates[2]. Apcin has been widely used in mitosis research to induce lethal mitotic arrest and cell death[3].
In vitro, Apcin treatment for 48 hours significantly inhibited the viability of A375 and HeLa cells, with IC50 values of 193.3µM and 220.8µM, respectively[4]. Incubating MG63 and U2OS cells with 75µM Apcin for 48 hours induced apoptosis, accompanied by an increase in the expression of pro-apoptotic molecules Bim and p21[5]. Treatment with 100µM Apcin for 48 hours suppressed the migration and proliferation of Z138 cells, promoted G2/M phase arrest of the cells, and reduced the expression of MMP2 and MMP9[6].
In vivo, Apcin treatment via intraperitoneal injection at a dose of 5mg/kg/day for 5 days alleviated the renal dysfunction and tubular damage in mice with acute kidney injury induced by cisplatin[7]. In a unilateral urinary tract obstruction mouse model, intraperitoneal injection of Apcin (1mg/kg/day) for 8 consecutive days reduced collagen deposition and fibrotic lesions in the renal interstitium and inhibited the expression of inflammatory factors[8]. Intraperitoneal injection of Apcin at a dose of 30μM/kg, every other day for 16 consecutive days, markedly suppressed tumor growth in KLE xenograft mice without affecting body weight[9].
References:[1] He Y, Le X, Hu G, et al. Discovery of ureido-based apcin analogues as Cdc20-specific inhibitors against cancer[J]. Pharmaceuticals, 2023, 16(2): 304.
[2] Sackton K L, Dimova N, Zeng X, et al. Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C[J]. Nature, 2014, 514(7524): 646-649.
[3] De Lange J, Faramarz A, Oostra A B, et al. Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function[J]. Nature communications, 2015, 6(1): 8399.
[4] Huang P, Le X, Huang F, et al. Discovery of a dual tubulin polymerization and cell division cycle 20 homologue inhibitor via structural modification on apcin[J]. Journal of Medicinal Chemistry, 2020, 63(9): 4685-4700.
[5] Gao Y, Zhang B, Wang Y, et al. Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells[J]. Oncology reports, 2018, 40(2): 841-848.
[6] Chen Y, Yang P, Gao S, et al. Inhibition of CDC20 suppresses the development and progression of mantle cell lymphoma through PI3K/AKT pathway[J]. Annals of Hematology, 2026, 105(4): 169.
[7] You R, Li Y, Jiang Y, et al. WWP2 deletion aggravates acute kidney injury by targeting CDC20/autophagy axis[J]. Journal of Advanced Research, 2025, 71: 471-485.
[8] He J, Xu S, Jiang M, et al. CDC20 inhibition alleviates fibrotic response of renal tubular epithelial cells and fibroblasts by regulating nuclear translocation of β-catenin[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2023, 1869(4): 166663.
[9] Ni K, Li Z, Hu Z, et al. Antitumor effect of apcin on endometrial carcinoma via p21-mediated cell cycle arrest and apoptosis[J]. Current Medical Science, 2024, 44(3): 623-632.